The Laboratory of Bioengineering and Physical Science is supports the NEI in three projects that require innovative and independent optical design approaches to address the unique requirements of clinical and basic research studies.[unreadable] [unreadable] The first instrument assesses the level of the carotenoid pigments, lutein and zeaxanthin, present in the human macula. These pigments protect against age-related macula degeneration, the leading cause of blindness in the elderly. Resonance Raman spectroscopy is a non-invasive methodology that allows quantification of these macular pigments in the retina.[unreadable] [unreadable] The Resonance Raman Spectrometer, which was developed at the University of Utah, requires an alignment procedure to be carried out by the patient prior to initiating the laser pulse that produces the backscattered Raman signal from the patient's retina. This alignment is a simple matter with patients who possess good visual acuity, but degeneration of the macula makes the alignment a difficult problem. To overcome this problem, the instrument was modified to provide a video presentation of the subject's eye centered on the cornea. A low-level helium-neon laser was introduced into the instrument's optical path co-linear with the optical axis of the Raman excitation and emission pathways. The video camera captures the scattered and reflected laser beam from the front surface of the cornea. The physician adjusts the position of the subject's eye until the laser beam is centered on the cornea. This is accomplished by orienting to fiducial marks and by the increase in reflected intensity as the front surface of the cornea becomes perpendicular to the incident alignment laser beam. Clinical trials using the new instrumentation have shown an increase, from a few successful images per run to almost a 100% success rate, in the ability to gather data.[unreadable] [unreadable] A second application is the modification of a fundus camera to capture an electro-retinogram following laser stimulation of selected areas of the retina and to photograph the selected area. There are five main components to this optical system. First, a helium neon laser (633 nm) was made collinear and coincident with an argon ion laser (488 nm) or triggered xenon flashlamp and serves as a surrogate light beam during patient alignment for the electro-retinogram stimulating pulsed argon laser or xenon flashlamp. Second, within the parallel light space of the optical path, a variable aperture can be freely positioned laterally to the light path such that it allows the physician to adjust the size and position of the area of illumination on the retina. Third, a final focusing lens of appropriate focal length and f-number is chosen to cover a maximum area (i.e. at full aperture), after reaching a focus at the lens of the eye, equivalent to the optic nerve. Fourth, a glass beamsplitter introduces the modified optical path of the surrogate and stimulating lasers into the optical path of the fundus camera, such that both pathways are coincident. Fifth, a vertical polarizer is introduced into the laser path prior to the beamsplitter and a second horizontal polarizer is introduced into the observation pathway of the fundus camera. The significance of this is that it allows depolarized light from the retina to be observed, but eliminates unwanted specular reflections from optical surfaces, most particularly the cornea. Rotation of either polarizer renders this reflection visible, if required. A preliminary clinical evaluation is on-going to capture ERG responses in normal and diseased areas of the retina. A provisional patent application (60/935107) "A Fundus photostimulation system and method" is ongoing.[unreadable] [unreadable] A Ganzfeld-type illumination system has been constructed to permit uniform illumination of the visual field of small animals. A 12-inch diameter sphere was modified to accommodate the animal support platform and associated recording electrodes, and internally coated with reflective paint. Fiber optic coupling to the reflecting sphere introduced the stimulating light from a commercial source. This instrument is currently under development.